U.S. APPROVES SALE OF IMPOTENCE PILL; HUGE MARKET SEEN

After months of eager anticipation by patients, doctors and investors, the Food and Drug Administration yesterday approved the first pill for male impotence.

The prescription drug, sildenafil citrate, or Viagra, made by Pfizer Inc., is taken about an hour before intercourse and was found in studies to help 70 to 80 percent of impotent men. It acts on the normal physiological system in the penis and elicits an erection when a man is sexually stimulated; it has no effect if he is not.

Pfizer scientists discovered the erection-producing effect of the compound by accident six years ago and leapt to develop the drug as soon as they realized what they had.

The company announced yesterday that Viagra would be available by mid-April at a wholesale price of $7 a pill. At that price, securities analysts said, consumers will wind up paying $8.50 to $9 a pill.

In anticipation of the F.D.A. approval, and in expectation that resulting Viagra sales would quickly soar to several billion dollars a year, investors have pushed the price of Pfizer shares up 21 percent in the last two months. [Page D1.]

Although discussion of impotence may evoke nervous titters, urologists say it is no laughing matter. Pfizer said that 30 million American men were afflicted, and a large study in Massachusetts has found that half of all men between the ages of 40 and 70 have problems getting or maintaining an erection.

''The prevalence is stunning,'' said Dr. Ridwan Shabsigh, a urologist who directs the New York Center of Human Sexuality at Columbia-Presbyterian Medical Center.

The other remarkable thing, said Dr. Shabsigh, whose entire practice is devoted to treating impotence, is that fewer than 10 percent of impotent men seek treatment.

Many, he said, deal with it like a secret shame, embarrassed to tell a doctor. Others assume that the problem is an entrenched psychological one that would be difficult to resolve, or that it is a normal consequence of aging.

There were a number of impotence treatments before Viagra, but all carried one or more drawbacks that the drug will not have: a need for surgery, interruption of lovemaking, or pain.

In one available treatment, rigid prostheses are implanted in surgery, producing erections that are ''not very natural,'' said Dr. Harin Padma-Nathan, an impotence specialist in Los Angeles. In another, the patient himself inserts suppositories into the end of the penis with a tiny plunger. Then there are injections, like those tried by Michael Bierly, a 64-year-old Los Angeles lawyer, whose impotence began three years ago after surgery for prostate cancer.

''When you're diagnosed with this kind of disease, you're absolutely devastated,'' Mr. Bierly said, and so, although he knew that impotence might result from the cancer surgery, it hardly peeked over the horizon of his concerns.

Later, when he discovered that he could no longer have intercourse, he felt desolate and frightened. But he kept his suffering to himself. ''It wasn't a problem that guys discussed,'' he said.

Eventually Mr. Bierly tried injections of chemicals that can force a flaccid penis to become erect.

''It simply didn't work,'' he said. ''It was cumbersome and painful. I was clumsy -- you have to mix things up, and that took me 10 or 15 minutes. By the time I get done, she's asleep.''

One time his erection lasted five hours despite intercourse during the interim. ''I would have gone to the emergency room,'' he said, ''but I didn't know what I would tell them.''

Mr. Bierly participated in Pfizer's clinical tests of Viagra, and the drug worked for him.

''It is the most natural thing in the world,'' he said.

Dr. Ian Osterloh, who directed development of Viagra for Pfizer, said it was initially conceived as a drug to alleviate angina, the chest pains caused by the blocking of blood vessels that lead to the heart. That effort proved disappointing: the company began small pilot studies in 1991, and by the end of 1992 was ready to abandon the drug.

There was, however, one unusual finding: some men, asked to report side effects, said they were having erections.

''At the time, it was more a curiosity than anything else,'' Dr. Osterloh said, since the researchers had no idea whether the men reporting the erections had previously been impotent. ''They were not very forthcoming,'' Dr. Osterloh said.

But soon afterward Pfizer researchers noticed a scientific paper that said nitric oxide, a short-lived chemical that is released from nerve endings in the penis, was important in creating erections. Knowing how Viagra worked, ''we began putting two and two together,'' Dr. Osterloh said, and the Pfizer scientists soon suspected that there was a reason the men were reporting erections: Viagra just might be alleviating impotence.

The physiology behind the workings of Viagra is this:

When a man is sexually stimulated, his brain sends signals to the nerves surrounding the penis. Those nerve cells release nitric oxide, which in turn causes the penis to make another chemical, cyclic guanosine monophosphate, or cyclic GMP.

Cyclic GMP, also referred to as cGMP, is the key to having an erection. It widens blood vessels in the penis, and so blood gushes in, causing the penis to become rigid.

As long as a man remains sexually stimulated, he continues to produce cyclic GMP. But at the same time he makes another chemical, phosphodiesterase 5, or PDE5, which destroys cyclic GMP. The result is an equilibrium: the production and degradation of cyclic GMP are in balance, and the penis remains erect. When the sexual stimulation ends, cyclic GMP stops being produced and PDE5 takes over, destroying the left-over chemical. The erection disappears.

Viagra blocks PDE5. If a man who is impotent takes the drug, it boosts the effects of cyclic GMP in his penis by slowing its degradation. The result can be an erection in a man who would not normally be able to have one.

Moreover, Dr. Osterloh said, Pfizer researchers ultimately discovered that PDE5 is not an important enzyme elsewhere in the body -- in the coronary arteries, for example. That is why Viagra did not alleviate angina. So Viagra might, by a stroke of dumbfounding luck, happen to be active only in the penis, and only when a man is sexually aroused.

Toward the end of 1993, Pfizer began testing Viagra as an impotence drug. The company eventually completed 21 clinical studies involving more than 3,000 men. The subjects had been impotent for an average of five years and had disorders like diabetes, high blood pressure, spinal cord injuries or psychological difficulties, or had undergone prostate cancer surgery, which usually leaves men impotent.

Viagra was effective in 70 percent to 80 percent of the men who took it, Dr. Osterloh said. In contrast, erections were experienced by 6 percent to 20 percent of those who took a dummy pill. (Those whose impotence was caused by severe physiological occurrences like prostate surgery or diabetes were least likely to respond to placebos; those whose impotence was psychological were most likely to respond.)

The most common side effect was headaches, afflicting 16 percent of those who took Viagra, compared with 4 percent of those who took a placebo. Other side effects included flushing, indigestion, a stuffy nose and, among 3 percent of the Viagra patients, a mild bluish tinge imposed on their vision that lasted a few minutes to a few hours.

When Pfizer, having found success in its clinical studies, tried to bring them to a conclusion, subjects wrote to the company in droves, begging to be allowed to keep a supply of pills. The company complied.

As word of Viagra leaked out, patients began peppering their doctors with questions about it: When would they be able to get it? What was it like?

''Virtually every patient I see that has any sort of impotency problem, even men who are able to function sexually but who want to function better, want it,'' said Dr. William J. Catalona, chief of urology at Washington University in St. Louis.

Mr. Bierly, the patient who previously used injections, said that while he was participating in Pfizer's studies, his friends constantly asked him to slip them some Viagra pills. He refused, he said, but is constantly amazed at the number of men who want the drug. ''It makes me think the problem is more prevalent than I thought,'' he said.

Doctors caution that Viagra will not make normal men sexual virtuosos. There is no reason to believe that it will revive flagging sex drive, or allow men to partake in sexual endurance feats.

''This drug does not alter libido or desire,'' Dr. Padma-Nathan said. ''It does not create prolonged erections. And if you have normal erections, it will not make you feel more rigid.''